Diphosphonates remain among the most common drug treatments for osteoporosis. Recent evidence has implicated diphosphonate therapy, specifically, alendronate, with low-energy fractures of the subtrochanteric region of the femur. The general conclusion is that prolonged suppression of bone remodelling with alendronate may be associated with a new form of insufficiency fracture of the femur.

Three case reports of patients with alendronate related insufficiency are discussed here with their treatment modalities and lessons learnt. One of the three patients had bilateral subtrochanteric stress fracture. A comprehensive review of the literature is presented with the best evidence for investigating, treating and preventing these fractures

Our experience in Launceston has increased awareness amongst the local medical community regarding the long term use of Diphosphnates and the fractures they may cause. Changes to our practice have included: Increased suspicion of patients with hip pain on diphosphonate therapy, imaging the contralateral femur to rule out stress fractures, reassuring GP's and Patients that benefits of Diphosphonate therapy far outweigh the potential risks.

There are many unresolved questions about the prolonged use of diphosphonates, but there is sufficient evidence to show subtrochanteric stress fractures do occur. We, as Orthopaedic Surgeons, must be able to recognize this new entity and educate our medical colleagues appropriately.

This paper discussed the challenges to provide advanced surgical training in orthopaedics, the inter-relationship between trainers, trainees, the AOA and the College. It looks at the factors that are involved in each level of training, some of the new initiatives that are being undertaken and the medicolegal issues regarding training of the modern generation of Orthopaedic trainees. It also discusses the pitfalls in process, that are present for all those involved in the training.

Antibiotics are frequently administered prophylactically in spinal procedures to reduce the risk of disc space infection. There is still controversy, however, over which antibiotics are able to penetrate the intervertebral disc effectively and whether the charges on the antibiotics are important in determining their ability to diffuse into the negatively charged intervertebral disc.

In a prospective randomised double blind clinical study, we examined the penetration of two commonly used antibiotics, cefuroxime (negatively charged) and gentamicin (positively charged), into the intervertebral discs. Twenty patients, randomised into two separate groups, received either 1.5g cefuroxime or 5 mg/kg gentamicin prophylactically two hours before their intervertebral discs removed. A blood specimen, from which serum antibiotic levels were determined, was obtained simultaneously with each discectomy.

Clinical therapeutic levels of antibiotic were detectable in the intervertebral discs of all the ten patients who received gentamicin. Only two of the ten patients (20%) who received cefuroxime had quantifiable level of antibiotic in their discs even though serum levels of cefuroxime were at therapeutic levels in all ten patients. Our results showed that cefuroxime does not diffuse into human intervertebral discs as readily as gentamicin and suggest that the charge due to ionisable groups on the antibiotics is important in determining the penetration of antibiotics. We therefore recommend the use of gentamicin in a single prophylactic dose for all spinal procedures to reduce the incidence of post-operative discitis.

Antibiotics are often administrated prophylactically in spinal procedures to reduce the risk of infection of the disc space. It is still not known which antibiotics are able to penetrate the intervertebral disc effectively. In a prospective, randomised, double-blind clinical study, we examined the penetration of the intervertebral discs of two commonly used antibiotics, cefuroxime and gentamicin. The patients, randomised into two groups, received either 1.5 g of cefuroxime or 5 mg/kg of gentamicin prophylactically two hours before their intervertebral discs were removed. A specimen of blood, from which serum antibiotic levels were determined, was obtained at the time of discectomy.

Therapeutic levels of antibiotic were detectable in the intervertebral discs of the ten patients who received gentamicin. Only two of the ten patients (20%) who received cefuroxime had a quantifiable level of antibiotic in their discs although therapeutic serum levels of cefuroxime were found in all ten patients. Our results show that cefuroxime does not diffuse into human intervertebral discs as readily as gentamicin. It is possible that the charge due to ionisable groups on the antibiotics can influence the penetration of the antibiotics. We therefore recommend the use of gentamicin in a single prophylactic dose for all spinal procedures in order to reduce the risk of discitis.

Our aim was to investigate whether nitric oxide synthase (NOS) isoforms, responsible for the generation of NO, are expressed during the healing of fractures. To localise the sites of expression compared with those in normal bone we made standardised, stabilised, unilateral tibial fractures in male Wistar rats. Immunostaining was used to determine the precise tissue localisation of the different NOS isoforms. Western blotting was used to assess expression of NOS isoform protein and L-citrulline assays for studies on NOS activity. Control tissue was obtained from both the contralateral uninjured limb and limbs of normal rats.

Immunohistochemistry showed increased expression of endothelial NOS (eNOS) to be strongest in the cortical blood vessels and in osteocytes in the early phase of fracture repair. Western blot and image analysis confirmed this initial increase. Significantly elevated calcium-dependent NOS activity was observed at day 1 after fracture.

Inducible NOS (iNOS) was localised principally in endosteal osteoblasts and was also seen in chondroblasts especially in the second week of fracture healing. Western blotting showed a reduction in iNOS during the early healing period. Significantly reduced calcium-independent NOS activity was also seen. No neuronal NOS was seen in either fracture or normal tissue.

Increased eNOS in bone blood vessels is likely to mediate the increased blood flow recognised during fracture healing. eNOS expression in osteocytes may occur in response to changes in either mechanical or local fluid shear stress. The finding that eNOS is increased and iNOS reduced in early healing of fractures may be important in their successful repair.

Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption.

We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E₂ (PGE₂), as an indicator of COX-2 activity, was measured using an enzyme immunoassay.

Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68⁺ macrophages.

The presence of calcium-independent iNOS activity and PGE₂ production was confirmed in the homogenized interface membrane. Immunocytochemistry showed that periprosthetic CD68⁺ wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68⁺ macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68⁺ macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and have been implicated in the induction and PGE₂ maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening.

We have studied the ability of a range of antibiotics to penetrate intervertebral disc tissue in vitro, using a mouse disc model. Equilibrium concentrations of antibiotics incorporated into the entire disc were determined by bioassay using a microbial growth-inhibition method. Uptake was significantly higher with positively-charged aminoglycosides compared with negatively-charged penicillins and cephalosporins. Uncharged ciprofloxacin showed an intermediate degree of uptake. Our results support the hypothesis that electrostatic interaction between charged antibiotics and negatively-charged glycosaminoglycans in the disc is an important factor in antibiotic penetration, and may explain their differential uptake.

Six boys with fragmentation of the proximal pole of the patella are reported; the condition was bilateral in one. Four of the six presented with symptoms of Osgood-Schlatter's disease or Larsen-Johansson disease of the same or of the contralateral knee, but they had no symptoms or signs relating to the proximal pole of the patella; one also had features suggesting minimal chondromalacia patellae. Two boys had no objective abnormality in either knee. It is suggested that the fragmentation may be a further form of traction osteochondritis of the attachments of the quadriceps mechanism. Attention is drawn to its characteristic radiographic appearance, its association with other forms of juvenile traction osteochondritis (which are commonly symptomatic), and to its occurrence in boys aged 10 or 11 years.